Influence of the linker in bispyridium compounds on the inhibition of human choline kinase

J Med Chem. 2004 Oct 21;47(22):5433-40. doi: 10.1021/jm0496537.

Abstract

Studies have been aimed to establish the structure-activity relationship that define choline kinase (ChoK) inhibitory potency and antiproliferative activity of a set of 25 bispyridinium compounds with electron-releasing groups at position 4. Here we report that, according to their inhibitory activities against human ChoK, the enzymatic inhibitory potency is closely related to the size of the linker, the 3,3'-biphenyl moiety being the most suitable. The N-methylanilino and its derivatives, 4-chloro-N-methylanilino and 3,5-dichloro-N-methylanilino, render higher ChoK inhibitory and antiproliferative activities against the HT-29 human colon cancer cell line.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Benzene Derivatives / chemical synthesis
  • Benzene Derivatives / chemistry
  • Benzene Derivatives / pharmacology
  • Biphenyl Compounds / chemical synthesis
  • Biphenyl Compounds / chemistry
  • Biphenyl Compounds / pharmacology
  • Cell Line, Tumor
  • Choline Kinase / antagonists & inhibitors*
  • Cyclopropanes / chemical synthesis
  • Cyclopropanes / chemistry
  • Cyclopropanes / pharmacology
  • Drug Screening Assays, Antitumor
  • Humans
  • Pyridinium Compounds / chemical synthesis*
  • Pyridinium Compounds / chemistry
  • Pyridinium Compounds / pharmacology
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Benzene Derivatives
  • Biphenyl Compounds
  • Cyclopropanes
  • Pyridinium Compounds
  • Choline Kinase